Grant: CIHR New Investigator

Schizophrenia and bipolar disorder affect hundreds of thousands of Canadians and their families. Both disorders are associated with a high risk of suicide. Several studies provide evidence that genetic factors influence suicidal behavior. The major aim of this study is to identify changes in the genetic material that are inheritable but are sensitive to environment and which genes and neurotransmitters are relevant to suicidal behavior. Understanding these factors might enable prediction of suicidal behavior in patients with schizophrenia and bipolar disorder. In this study, we will analyze proteins in the brain that influence transfer of information in different brain circuits. The instructions for creating these proteins are encoded in genes, but how these genes express themselves can be influenced by the environment through epigenetic modifications. We have collected genetic samples as well as detailed clinical information about suicide attempts and suicidal behavior severity scores from 336 bipolar and 497 schizophrenia patients. We will assess whether epigenetic modification is found in the genetic material and has occurred under the influence of external factors such as stress, medications and disease course. Additionally, we will estimate the gene activity of neurotransmitter receptors that are the target of antidepressants and antipsychotics. This analysis will be performed in 165 post-mortem brains donated by the Stanley Foundation including 41 patients who died by suicide. The genetic risk markers for suicide that we hope to identify could, in the future, identify persons at risk and thus facilitate preventive measures such as counseling, family education, and early treatment intervention for these individuals. Furthermore, the identified genes and genetic changes may reveal possible chemical imbalance in the brain of patients who have committed suicide which can be used as targets for development of novel medications for suicide prevention.